Calcitonin was discovered in 1961 and has been widely used clinically for the treatment Paget's disease, hypercalcemia, osteoporosis, and the relief of bone pain. Calcitonin is a hormone produced by the thyroid gland and secreted in response to high levels of calcium in the blood. Also known as thyrocalcitonin, it lowers the level of calcium in the blood by inhibiting bone resorption, the dissolution of bony tissue. Calcitonin plays a role in pain relief and has been noted for its analgesic effects in bone metastases of primitive cancer and phantom limb pain. It can also enhance or produce recalcification, and is the subject of studies for treatment of peptic ulcers. Though a wide range of pharmacological effects have been attributed to calcitonin, discussion of calcitonin is generally associated with its effectiveness in treating pain and osteoporosis.
Copp reported discovering in addition to parathyroid hormone (PTH), which plays a key role in controlling hypocalcemia by stimulating osteolysis, a second calcium-regulating hormone, calcitonin. Copp found that hypercalcemia and lowered plasma calcium, by inhibiting osteolysis, released calcitonin. Copp was involved in the isolation of salmon calcitonin, which is the form most widely used in therapy because of its high potency. In addition to inhibiting bone resorption, salmon calcitonin is a powerful analgesic agent with a potency in certain circumstances which is 30 to 50 times that of morphine. It is widely used clinically for the treatment of Paget's disease, hypercalcemia, osteoporosis, and relief of bone pain. World sales in 1992 exceeded U.S. $900 million, of which 85% was for osteoporosis. Copp, D. H., “Calcitonin: discovery, development, and clinical application,” Clin. Invest. Med., Vol. 17(3), pp. 268-77 (1994).
Osteoporosis is the thinning of bones with reduction in bone mass due to depletion of calcium and bone protein. Osteoporosis predisposes a person to fractures, which are often slow to heal and heal poorly. It is more common in older adults, particularly post-menopausal women, in patients on steroids, and in those who take steroidal drugs. Unchecked, osteoporosis can lead to changes in posture, physical abnormality (particularly in the form of a hunched back known colloquially as “Dowager's Hump”), and decreased mobility. The Food and Drug Administration (“FDA”) has announced approval of calcitonin salmon nasal spray for the treatment of osteoporosis. Prior to this approval, only injectable calcitonin salmon and estrogen had been approved to treat or prevent osteoporosis. The FDA reported two randomized clinical trials that demonstrated the daily use of calcitonin nasal spray increases bone mass in the spine. The FDA warns, however, that patients using the nasal spray should have periodic nasal examinations for ulceration or irritation. The most common adverse events reported during clinical trials included rhinitis (inflammation of the membranes in the nose), nosebleeds, and sinusitis (inflammation of the sinus cavity). The FDA emphasized that women on drug therapy for osteoporosis should take daily supplements of calcium and vitamin D. This regimen, along with exercise, has been shown to help prevent the loss of bone mass. Calcitonin salmon nasal spray is manufactured by Sandoz Pharmaceuticals Corp. of East Hanover, N.J., and is marketed under the trade name Miacalcin Nasal Spray. See “FDA Approves New Drug Therapy for Osteoporosis” (1995), available at http://www.fda.gov/bbs/topics/ANSWERS/ANS00677.html.
The effect of space travel on calcitonin levels has been the subject of studies using rats flown on an 18-day shuttle flight. Upon landing, reduced calcitonin levels in the flight animals suggested that space flight disrupts calcium metabolism in animals. It is expected then that extended space flight will require a method of enhancing calcitonin in the bodies of the crew. Hatton, D. C., et al., “Calcium metabolism and cardiovascular function after spaceflight,” J. Appl. Physiol., Vol. 92(1), pp. 3-12 (2002).
It has been reported that salmon calcitonin administered for 14 days was more effective than indomethacin in preventing heterotopic ossification. Gunal, I., et al., “Prevention of heterotopic ossification after total hip replacement: a prospective comparison of indomethacin and salmon calcitonin in 60 patients,” Acta. Orthop. Scand., Vol. 72(5), pp. 467-9 (2001). Siamopoulou, reported possible beneficial effects of intranasal calcitonin on bone resorption and pain relief in juvenile idiopathic arthritis. Siamopoulou, A., et al., “Effects of intranasal salmon calcitonin in juvenile idiopathic arthritis: an observational study,” Calcif. Tissue Int., Vol. 69(1), pp. 25-30 (2001).
Calcitonin has been widely reported as effective in preventing pain in a variety of circumstances. Lyritis, et al., studied the analgesic efficacy of calcitonin suppositories in comparison with bed rest and paracetamol tablets on 40 patients who had recently suffered a non-traumatic osteoporotic vertebral fracture. The test resulted in all calcitonin-treated patients experiencing an overall statistically significant decrease of spinal pain. The pain relief allowed for early mobilization and gradual restoration of the locomotive functions in the calcitonin-treated non-placebo group. Salmon calcitonin suppositories appear to cause a dramatic decrease in spinal pain in patients with recent osteoporotic vertebral fractures and influenced the early mobilization and the gradual restoration of their locomotor functions. Lyritis, G. P., et al., “Analgesic effect of salmon calcitonin suppositories in patients with acute pain due to recent osteoporotic vertebral crush fractures: a prospective double-blind, randomized, placebo-controlled clinical study,” Clin. J. Pain., Vol. 15(4), pp. 284-9 (1999).
Calcitonin has also been reported as effective in treating chronic phantom pain. Simanski, et al., reported a decrease in pain intensity after treatment with five cycles of salmon calcitonin infusion on a patient who had suffered a traumatic right-side arm plexus lesion. TENS therapy five times per day showed no analgetic effect. The test was repeated with calcitonin-infusion therapy and after five I.V. cycles, the test was continued with 200 I.U. salmon calcitonin intranasal per day. The initial phantom pain intensity decreased but showed no long-term analgesia. Intravenous salmon calcitonin showed only short-term analgetic effect. Simanski, C., et al., “Therapeutic concept for preventing chronic phantom pain after traumatic brachial plexus lesion,” Unfallchirurg, Vol. 104(7), pp. 659-64 (2001) In another study of calcitonin on phantom limb pain, Wall reported that phantom limb pain is a tremendous source of morbidity and suggested that one or two doses of intravenous salmon calcitonin 200 I.U. may be an effective treatment. Wall noted that clinicians should be aware of the rare but severe hypersensitivity reactions that can occur with salmon calcitonin. Internasal calcitonin appears to be similar in efficacy to the parenteral formulation, at least in pain associated with vertebral crush fractures. Wall, G. C., et al., “Calcitonin in phantom limb pain,” Ann. Pharmacother, Vol. 33(4), pp. 499-501 (1999).
In a study of calcitonin versus cimetidine or De-Nol in gastric ulcer treatment, it was reported that only the calcitonin group experienced the moderate side effects of headache, nausea, and flushing. Nevertheless, the study suggests that calcitonin may be considered as a valid anti-ulcer drug in the peptic ulcer patients with concomitant rheumatological diseases especially with osteoporosis. Janke, A., et al., “Calcitonin versus cimetidine or De-Nol in gastric ulcer treatment. An endoscopically controlled trial,” Dtsch Z. Verdau Stoffwechselkr, Vol. 48(5), pp. 239-43 (1988).
It has been disclosed that treating a patient with electrical stimulation at acupuncture points known as the “Ring of Air,” can endogenously increase serum neurotensin levels in living human beings. See U.S. Pat. No. 6,233,489. It has also been disclosed that treating a patient with electrical stimulation at acupuncture points known as the “Ring of Fire” can increase serum dehydroepiandrosterone (DHEA) levels. See U.S. Pat. No. 5,109,847. Until now, however, there has been no known method of endogenously increasing calcitonin levels in a living human being in a manner similar to the “Ring of Air” or “Ring of Fire” electrical stimulation.